Summary: Introduction
Asthemajorsiteofxenobioticmetabolism,theliverplaysacentral
role in preventing accumulation of a wide range of compounds
by converting them into a form suitable for elimination. As the
process of xenobiotic metabolism requires multiple biochemical
transformations, and the fact that some intermediates mediate
toxic responses, the liver is potentially susceptible to injury1
during the act of performing its function. An improved
quantitative understanding of the balance between functional
xenobiotic metabolism and hepatic damage would be of great
utility in forming guidelines for safe exposure levels in both the
pharmaceutical and the toxicological contexts. In particular, the
ability to predict the toxicity profile of lead candidates2
is critical
to streamlining pharmaceutical drug development, and a better
understandingoftheonsetoflivertoxicityisanavenuetorealizing
the "personalized medicine" concept, wherein drugs are selected
and dosed in accordance with the genetics, active biomarkers, and
environment of the individual patient.3
Furthermore, improved